Comparative study of gastrointestinal tract and liver toxicity of ferrous sulfate, iron amino chelate and iron polymaltose complex in normal rats

Pharmacology. 2008;82(2):127-37. doi: 10.1159/000142728. Epub 2008 Jul 8.


Iron deficiency is a common worldwide problem leading to several morbidities including anemia. Although oral iron is the first choice in iron deficiency therapy, it may produce gastrointestinal (GI) and liver disorders. The aim of our study was to evaluate: (1) acute toxicity (LD(50)) in different oral iron compounds such as ferrous sulfate (FS), iron amino chelate (AC) and iron polymaltose complex (IPC) and (2) possible differences in early and late toxicity in the GI tract and liver between them.

Methods: Hematological variables, liver enzymes, oxidative stress markers (thiobarbituric-acid-reactive substances, reduced glutathione, catalase, glutathione peroxidase, CuZn superoxide dysmutase) in intestinal mucosa and liver homogenates, and morphological parameters (gross anatomy, histology) were evaluated in non-anemic rats.

Results: LD(50) was lower (p < 0.01) in FS versus iron AC and IPC. The liver enzymes were increased in the FS group (p < 0.05). The FS group presented gastric mucosal erosions and the iron AC group showed submucosal hemorrhages in the lower GI tract (colon and rectum) versus the IPC and control groups. In the small intestine, the villi/crypt ratio and goblet cells per villus were significantly (p < 0.01) reduced in the FS and iron AC groups versus IPC. The eosinophils per villus were increased (p < 0.01) in the FS and iron AC groups versus the IPC and control groups. Ferritin was elevated (p < 0.01) in the IPC group versus FS and iron AC in the small intestine and liver. The oxidative stress markers were all significantly (p < 0.01) altered in the FS and iron AC groups versus the IPC and control groups in the intestinal mucosa and liver.

Conclusion: FS exhibited important acute toxicity as well as early and late GI tract and liver toxicity. Despite showing similar LD(50) as IPC, iron AC presented differences regarding early and late GI tract and liver toxicity versus IPC.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Chemical and Drug Induced Liver Injury
  • Female
  • Ferric Compounds / administration & dosage
  • Ferric Compounds / toxicity*
  • Ferritins / drug effects
  • Ferritins / metabolism
  • Ferrous Compounds / administration & dosage
  • Ferrous Compounds / toxicity*
  • Gastrointestinal Diseases / chemically induced
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Iron Chelating Agents / administration & dosage
  • Iron Chelating Agents / toxicity*
  • Lethal Dose 50
  • Liver Function Tests
  • Male
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Toxicity Tests, Acute


  • Ferric Compounds
  • Ferrous Compounds
  • Iron Chelating Agents
  • ferrous sulfate
  • Ferritins
  • teferrol